Epilepsy affects approximately 42,000 children in the UK, but few anti-epileptic drugs (AEDs) go through paediatric clinical trials. Common side effects of AEDs are inability to concentrate, mild memory impairment and slowed motor skills. While these side effects affect both adults and children, in children they occur whilst the brain is still developing and may have lifelong implications. Adults who developed epilepsy as children have been found to have fewer educational qualifications and fewer job prospects. Importantly these long-term effects are also present in adults no longer taking AEDs indicating that the seizures or the AED treatment, or both, have permanently impaired development.

The cognitive side-effects of AEDs has not been fully researched, but Dr David Loring from the University of Florida has recently published a paper in the Psychiatric Times outlining what is currently known about the commonly prescribed AEDs.

Carbamazepine (Tegretol), phenytoin (Epanutin) and sodium valproate (Epilim) all have comparable side-effects - modest psychomotor slowing accompanied by decreased attention and memory. Treatment with carbamazepine has also been associated with EEG slowing in the alpha range which appears to be interlinked with cognitive decline.

Amongst the newer AEDs, gabapentin (Neurontin) has repeatedly been associated with good neuropsychological profiles with little or no cognitive impairment in studies of young adults. However, there is a degree of EEG slowing which, although less than that seen with carbamazepine, may be related to reduced IQ.

Lamotrigine (Lamictal) is also associated with little or no objective cognitive impairment. In one study over 50% of parents rated their children as improved in terms of attention span and alertness
when taking lamotigine. However lamotrigine has been used as an anti-depressant and it could be that a child's improved mood could influence assessment of cognitive functioning.

Levetiracetam (Keppra) appears to have a few cognitive side-effects, but has been reported to increase irritability and aggression. It also compares favourably with oxcarbazepine (Trileptal) and carbamazebine in terms of the affect it has on reaction time and unlike these other AEDs, levetiracetam was not associated with a change in any EEG or visual evoked potential parameter.

Oxcarbazepine, although structurally similar to carbamazebine appears to have fewer cognitive side effects, but there is still some EEG slowing.

Little research as been done on tiagabine (Gabitril), vigabatrin (Sabril) and zonisamide (Zonegran) although in one small study tiagabine was associated with a decline in verbal memory and energy levels.

Topiramate (Topamax) appears to have side-effects comparable to sodium valproate especially at high dosage levels and there has been a recent trend for lower dose use to counteract this.

There is an urgent need for more research in this field to determine which drugs offer children the best opportunity for improved quality of life in the short and long term.

Epilepsy Research UK, PO Box 3004, London W4 4XT Tel: (+44) (0) 20 8995 4781 • Fax: (+44) (0) 870 838 1069 Registered Charity No. 1100394